CLONING AND GENE MAP ASSIGNMENT OF THE XIPHOPHORUS DNA-LIGASE-1 GENE

Fishes represent the stem vertebrate condition and have maintained sev eral gene arrangements common to mammalian genomes throughout the 450 Myr of divergence from a common ancestor. One such syntenic arrangemen t includes the GPI-PEPD enzyme association on Xiphophorus linkage grou p IV and human chromosome 19. Previously we assigned the Xiphophorus h omologue of the human ERCC2 gene to linkage group U5 in tight associat ion with the CKM locus. CKM is also tightly linked to the ERCC2 locus on human chromosome 19, leading to speculation that human chromosome 1 9 may have arisen by fusion of two ancestral linkage groups which have been maintained in fishes. To investigate this hypothesis further, we isolated and sequenced Xiphophorus fish genomic regions exhibiting co nsiderable sequence similarity to the human DNA ligase 1 amino acid se quence. Comparison of the fish DNA ligase sequence with those of other species suggests several modes of amino acid conservation in this gen e. A 2.2-kb restriction fragment containing part of an X. maculatus DN A ligase 1 exon was used in backcross hybrid mapping with 12 enzyme or RFLP loci. Significant linkage was observed between the nucleoside ph osphorylase (NP2) and the DNA ligase (L1G1) loci on Xiphophorus linkag e group VI. This assignment suggests that the association of four DNA repair-related genes on human chromosome 19 may be the result of chanc e chromosomal rearrangements.